Resolution Of Ulcers Research Articles

Effective Treatment of Severe Chronic Graft Versus Host Disease with a Combination of B-Cell Depletion and Tyrosine Kinase Inhibition

IntroductionChronic Graft Versus Host Disease (cGVHD) has a large impact on morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Therapeutic approaches for cGVHD are limited. Affected patients require long-term use of immunosuppressive drugs, mainly corticosteroids combined with a calcineurin inhibitor, which lead to severe side effects. Options for second line therapy are numerous but no consensus on the most favourable choice of agents has been reached. Both monotherapy with rituximab (Cutler, Miklos et al. 2006, Kharfan-Dabaja, Mhaskar et al. 2009, van Dorp, Resemann et al. 2011) and monotherapy with tyrosine kinase inhibition (Magro, Mohty et al. 2009, Olivieri, Locatelli et al. 2009) have shown to be effective in reducing cGVHD symptoms.Materials and MethodsWe performed a prospective study to test whether the sequential therapy of the anti-CD20 antibody rituximab followed by a 6 month treatment period with nilotinib, a tyrosine kinase inhibitor, is a favorable treatment strategy for patients with sclerotic cGVHD (EudraCT nr 2008-004125-42). All patients were evaluated monthly according to NIH cGVHD consensus response criteria working group recommendations from 2005. Serial blood sampling was performed every other month.ResultsWe included 29 patients, 5 patients went offstudy (1 with side effects rituximab, 2 with gastro-intestinal side effects nilotinib, 1 patient had progression of M. Hodgkin, 1 patient due to viral encephalitis with cognitive impairment), 24 are available for analysis. Baseline characteristics are depicted in table 1. We observed a response in 71% (2 patients CR, 15 patients PR). Only 1 patient showed progressive disease (PD) and the remaining 6 patients showed stable disease (SD). Moreover, 2 out of 5 patients who suffered from severe ulcerations at the start of the study had a complete resolution of ulcers at the end of the treatment period. Responding patients show a significant decrease in cGVHD affected body surface area (Figure 1) mostly explained by a significant reduction in nonmoveable sclerosis. Patients with a (partial) response also show a clinically relevant decrease in self attributed severity of cGVHD. On a scale of 10 points their self-attributed cGVHD severity decreased in the PD+SD group with a mean of 0,3 points whilst in the PR+CR group there was a mean decrease of 2,4 points. Fifty percent of responding patients could taper >50% of their daily prednisolone dose at the end of the study period. Other immunosuppressive drugs (ciclosporin, MMF) could also be tapered. Rituximab was well tolerated except for 1 patient who showed a neurological syndrome resembling Guillain Barre after 2 infusions and therefor went offstudy. Nilotinib was dosed 300mg b.i.d. however only 9 patients tolerated this dose without side effects. For the remaining patients the dose was decreased to 200mg b.i.d. which was well tolerated for the majority. Most encountered side effects included fatigue, nausea, pain in extremities and prolonged QT-interval on standard ECG monitoring.ConclusionsThe combination of B-cell depletion and tyrosine kinase inhibition provides a new and interesting alternative treatment option for this difficult and heavily pretreated patient category. Approximately 70% of patients achieve a (partial) response with a decrease of sclerosis, an improved quality of life and a significant reduction in the use of corticosteroids. Two patients reached a complete resolution of all cGVHD related symptoms which is seldom achieved. How to prospectively designate which patients will benefit from this treatment strategy is currently under investigation. [Display omitted] [Display omitted] DisclosuresKuball:Gadeta B.V,: Membership on an entity's Board of Directors or advisory committees.

Combined application of nasogastric tubes and nasointestinal tubes in neurosurgical intensive care patients with stress ulceration: a novel solution to treatment and early enteral nutrition.

Objective Stress ulcers occur frequently in neurosurgical intensive care patients and can pose serious risks. We summarized the clinical experience of the combined application of nasointestinal tubes for early restoration of enteral nutrition and of nasogastric (NG) tubes for stress ulceration treatment in patients hospitalized in a neurosurgical intensive care unit.MethodsFrom January 2011 to June 2011, a series of 67 patients with stress ulceration hospitalized in a neurosurgical intensive care unit were randomized to two groups. The control group (33 patients) received treatment with NG tube decompression and drainage according to international guidelines, and parenteral nutrition was changed to enteral feeding until there was no grossly visible blood in the NG tube. The nasointestinal tube group (34 patients) received treatment combining application of NG tubes and nasointestinal tubes. Drainage was performed with NG tubes as in the control group, with concurrent placement of nasointestinal tubes. Duration until resolution of stress ulceration and days until start of enteral nutrition were compared between the two groups.ResultsDuration until resolution of stress ulceration was 4.5 days in the control group and 4.3 days in the nasointestinal tube group. There was no difference between the two groups (P > 0.05). Duration until start of enteral nutrition was 4.5 days in the control group and 1 day in the nasointestinal tube group. There was an obvious difference between the two groups (P < 0.01).ConclusionsThe combined application of NG tubes and nasointestinal tubes in neurosurgical intensive care patients with stress ulceration is an effective means of treating stress ulceration and restoring early enteral nutrition.

Cyclosporine Rescue in Vedolizumab Patients with Steroid-Refractory Severe Ulcerative Colitis: A Case Series

Ulcerative colitis (UC) is characterized by relapsing and remitting episodes of colonic mucosal inflammation presenting as urgency, hematochezia, and abdominal pain. Approximately 20 to 30% of patients with UC will require colectomy for acute complications or for medically intractable disease. Patients who are primary or secondary nonresponders to anti-tumor necrosis factor medications may respond to anti-integrin therapy with vedolizumab (VDZ) or cyclosporine. We report a case series of 4 patients with steroid-refractory, TNF-nonresponders with severe UC who were treated with rescue intravenous cyclosporine during VDZ therapy. Four patients were admitted for cyclosporine infusion between 2015 and 2016. Prior to initiating cyclosporine, all patients were excluded for C. difficile infection and underwent flexible sigmoidoscopies. Cyclosporine infusion was given at a dose of 2 mg/kg for 7 days, titrated by level, with transition to an oral cyclosporine taper on discharge with continuation of VDZ maintenance or induction. All patients tolerated IV cyclosporine without major complications. The c-reactive protein level and Mayo score decreased in all patients. Patient 1 started VDZ 7 months prior to cyclosporine infusion with partial response. She was tapered off cyclosporine as an outpatient while continuing VDZ. After several months, she developed recurrent frequent loose bloody bowel movements. Patient 2 started VDZ 6 months prior to cyclosporine infusion. He responded well to cyclosporine and was tapered off as an outpatient while remaining on VDZ. Repeat colonoscopy 3 months post-cyclosporine demonstrated endoscopic healing. Patient 3 had been on IV steroids for 3 days before receiving cyclosporine, which led to complete resolution of blood in stool and diarrhea. She started VDZ two weeks after discharge and tapered off prednisone and cyclosporine. Colonoscopy after 2 months on VDZ revealed resolution or healing of most ulcerations. Patient 4 initially had a partial response to cyclosporine treatment. However, she soon developed recurrent bloody bowel movements with sigmoidoscopy showing severe inflammation and deep ulcerations. The patient ultimately underwent an ileal pouch-anal anastomosis. Treatment of patients with refractory severe UC remains difficult and controversial. We present 4 patients who received cyclosporine with VDZ. Two patients demonstrated endoscopic healing. There were no adverse events or serious infections in this series.

Helicobacter heilmannii Gastritis: Is Your Pet to Blame?

Introduction: H. heilmannii is a spiral bacilli of Helicobacter family generally found in primates, cats, pigs, and carnivorous mammals. Rare incidences of infection in human populations have been reported. The bacterium usually induces mild chronic gastritis but is infrequently associated with peptic ulceration and rarely with gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. We report a case of H. heilmannii chronic gastritis.Figure 1Case: A 60 year female with past medical history of gastro esophageal reflux disease presented with epigastric discomfort along with nausea and two episodes of non-bloody vomiting. She had quit smoking many years ago and was not using NSAIDS. She lived at home with her husband and her dog. Mild epigastric tenderness was notable on examination and lab work was normal including a normal serum gastrin level. Mild fatty infiltration of the liver was evident on ultrasound and CT abdomen showed thickening and edema of the antrum and duodenal bulb. Endoscopy revealed multiple antral ulcers with surrounding edema with some ulcers having black eschar at the base. There were several linear ulcers in the second portion of duodenum. Biopsy showed marked reactive inflammatory changes without metaplasia. Immunohistochemical staining pattern was consistent with H.Heilmannii. She received 6 weeks of anti- H Pylori triple therapy. A follow up endoscopy showed resolution of ulcers with biopsy negative for the organism. Discussion: Helicobacter species other than H. pylori are also referred to as H. heilmannii-like organisms (HHLO's). These long tightly coiled bacteria residing in the stomach of hosts such as cats, dogs, and pigs. Studies suggest the transmission of HHLO's through these pet's saliva. H. heilmannii infection has been associated with peptic ulcer disease, gastric carcinoma, and gastric MALT lymphoma in humans. Most cases present with antral predominant gastritis. Interestingly some studies have also shown that incidence of MALT lymphomas is higher in patients with HHLO gastritis as compared to patients with H.Pylori gastritis making them a significant health challenge. Sensitivity of diagnostic tests, such as rapid urease test, urea breath test and blood antibody is not high for HHLOs. Due to variation in morphology with in same species PCR is more accurate diagnostic test compare to histology. Treatment is a course of triple therapy with emphasis on measures to prevent reinfection from pets.

Critical Evaluation of Delayed Healing of Venous Leg Ulcers: A Retrospective Analysis in Canadian Patients.

Venous leg ulcers (VLUs) are common but challenging health problems. Better understanding of the risk factors involved in delayed healing of VLUs may therefore guide individualized treatment plans to improve patient outcomes. We sought to identify the risk factors associated with delayed healing of VLUs in patients seen at a tertiary academic wound care clinic. A retrospective analysis of 554 patients who presented to the Toronto Regional Wound Healing Clinic for VLUs in a 3-year period was performed. Patient and ulcer characteristics were recorded. Multivariate analyses were performed to compare patients with ulcer resolution and those whose ulcers did not resolve after 12-month follow-up. The average age of the patients was 67.3 ± 0.7 years, with 56% being female. The most common comorbidities were hypertension (54%), dyslipidemia (33%), a history of smoking (30%), and diabetes (26%). Ulcer resolution was associated with a smaller ulcer size (odds ratio [OR] 0.984 [95% confidence interval (CI) 0.973, 0.996]), shorter ulcer duration (OR 0.704 [95%CI 0.574, 0.865]), and dyslipidemia (OR 1.848 [95%CI 1.052, 3.246]). Pro-healing factors associated with VLUs were a smaller ulcer size and a shorter ulcer duration. Dyslipidemia was also associated with improved healing, potentially owing to the use of statins. Patients presenting with poorer-prognosis VLUs should receive more aggressive treatment with earlier referral to vascular surgery.

Platelet-rich plasma (PRP) and adipose-derived mesenchymal stem cells: stimulatory effects on proliferation and migration of fibroblasts and keratinocytes in vitro.

The clinical use of tissue engineering associated with cell therapy is considered a new alternative therapy for the repair of chronic lesions with potential application in different medical areas, mostly in orthopedic and dermatological diseases. Platelet-rich plasma (PRP) is a rich source of growth factors and cytokines important for wound healing. Adipose-derived mesenchymal stem cells (ADSCs) have shown potential to accelerate the resolution of ulcers, to stimulate cell proliferation, and to benefit the quality of skin repair. This study aims to determine the effect of PRP and conditioned medium (CM) from ADSC on fibroblast and keratinocyte proliferation in vitro. Migration and proliferation assays were performed to evaluate the growth of fibroblasts and keratinocytes in the presence of PRP, CM, and CM+PRP. Significant proliferative stimulation was observed after 48h of culture (p<0.05) on mean absorbance of fibroblasts cultured with 10 and 25% PRP, 100% CM, and 25% PRP+25% CM, if compared with control. Keratinocyte proliferation was stimulated after 48h in cultures with 25, 50, and 100% CM, and growth was compared with controls. The migration assay detected a significant migratory stimulus in fibroblasts cultured with 10% PRP+10% CM after 48h. These in vitro results suggest that PRP and ADSC have therapeutic potential for healing and re-epithelialization of chronic wounds in vivo.

SS13. Ulcer Healing and Quality of Life Outcomes in Endovascular Iliocaval Reconstruction for Patients With Concomitant Inferior Vena Cava and Iliac Occlusive Disease

The purpose of the study is to report outcomes of endovascular iliocaval reconstruction in those patients with chronic concomitant inferior vena cava and iliac vein occlusive disease. These patients require complete endovascular recanalization of the inferior vena cava and the iliocaval confluence for C4-C6 disease treatment. Current outcomes data for this patient population are limited in scope. A prospectively maintained retrospective single-institution database was used to identify patients with C4-C6 disease who underwent endovascular iliocaval reconstruction with self-expanding Elgiloy stents for concurrent IVC and iliac vein occlusive disease. The Villalta clinical scoring system for post-thrombotic syndrome was used to assess symptom improvement pre- and postoperatively. Postoperatively, patients with C6 venous disease underwent continued compression therapy and were monitored for wound healing. Forty-six patients underwent endovascular iliocaval reconstruction for symptomatic (C4-C6) concurrent inferior vena cava and iliac vein occlusive disease between 2014 and 2016. Thirty-two (70%) patients had prior placed IVC filters. Technical success was 100%, with primary patency achieved in all patients. There were no significant intraoperative complications, and 30-day mortality was zero. An average of 4.5 stents were used per patient. At follow-up intervals of 3, 6, and 12 months, primary patency was 100%, 93.6%, and 84.9%, respectively. Secondary patency at 12 months was 93.6%. Symptomatic and sustained improvement was seen in all patients as measured by the Villalta clinical scoring system for post-thrombotic syndrome, with an average decrease in Villalta score of 16.46 ± 3.89 by 3 months. Twenty-one patients had C6 venous disease, with ulcers present on 30 limbs due to the presence of bilateral disease. The average ulcer had been present for 15.8 months. Twenty-three limbs had complete ulcer resolution during the follow-up period. The remaining 7 limbs demonstrated >60% ulcer size reduction. Endovascular iliocaval reconstruction appears to be a safe and effective approach for the treatment of chronic iliocaval occlusive disease. These procedures can be performed with excellent patency, minimal morbidity, improved Villalta scores and improved wound healing.

A Comparison Between Omeprazole and a Dietary Supplement for the Management of Squamous Gastric Ulceration in Horses

Although several studies have assessed the short-term effect of dietary supplements on the treatment and prevention of gastric ulceration in horses, few have assessed the response over a duration of more than 30 days. A blinded randomized noninferiority clinical trial was conducted using 42 Thoroughbred horses in race training with squamous ulceration of ≥ grade 2/4, randomly assigned to one of two treatment groups for a period of 90 days: omeprazole at the full label dose of 4 mg/kg or the Succeed digestive conditioning supplement. Noninferiority analyses and Wilcoxon sign rank tests were used to analyze the data. At day 90, Succeed was noninferior to 4 mg/kg omeprazole administered daily in terms of the proportion of horses with complete resolution of squamous ulceration. At day 30, Succeed was found to be inferior to omeprazole in terms of the proportion of horses with grade ≤1/4 squamous ulceration. The proportion of horses with reducing squamous ulcer score (compared with day 0) was statistically significant for both treatments at days 30 and 60. At day 90 of the 17 horses on Succeed, nine had a reducing squamous ulcer score (P value = .049), and of the 19 horses on omeprazole, 10 had a reducing squamous ulcer score at day 90 (P value = .091). The noninferiority of Succeed compared to omeprazole at 90 days for the complete resolution of squamous ulceration and the reduced efficacy of omeprazole following 90 days of treatment are likely to be of interest to practitioners managing gastric ulceration in performance horses.

Anti-TNFα treatment for recalcitrant ulcerative necrobiosis lipoidica diabeticorum: A case report and review of the literature

IntroductionNecrobiosis lipoidica diabeticorum (NLD) is a rare degenerative connective tissue disorder associated with diabetes mellitus, which usually presents with red papules or plaques with raised edges and occasional ulceration. Ulcerating NLD is notoriously difficult to treat. We present a young patient with ulcerative NLD who was successfully treated with the anti-TNFα agent infliximab. Case presentation is followed by a review of therapeutic TNFα blockade in NLD. Case presentationA 17-year old woman with type 1 diabetes since the age of 8, presented with a long-standing and extensively ulcerated and infected NLD lesion on her left shin. After achieving better glycemic control and treating her for infection of the wound, several NLD treatments failed to help, including corticosteroids and hyperbaric oxygen. She was treated successfully with 4 monthly sessions of 5mg/kg body weight intravenous infliximab, achieving complete resolution of ulceration. DiscussionA multitude of available treatments have been suggested for NLD over the past decades, based on two axes, one through wound healing and the other through immunosuppression. Anti-TNFα agents are relatively new drugs that brought a revolution in chronic inflammatory diseases and have been on the rise as novel potential treatments for NLD. Three out of the five available anti-TNFα agents have been safely tested so far, both topically and systematically, with mostly favorable results. ConclusionIntravenous infliximab was successful in the treatment of recalcitrant ulcerating NLD in our patient. Taken together with an increasing number of similar reports revealing a pathogenetic role of TNFα in NLD, we suggest that anti-TNFα agents are promising drugs in the management of this condition.

Oestrogen-soaked vaginal packing for decubitus ulcer in advanced pelvic organ prolapse: a case series.

Cervicovaginal decubitus ulceration is a well-known complication of advanced pelvic organ prolapse (POP). There is no consensus for its management. This case series describes the outcome of using repeated vaginal packs soaked with oestrogen cream to reduce POP and promote decubitus ulcer healing. We aimed to investigate the speed of ulcer healing and endometrial safety with this regimen. This was a retrospective study of patients with stage 3 or 4 POP and intact uterus with decubitus ulcer who were planned for surgery that included hysterectomy after ulcer healing. Vaginal packs are replaced at least biweekly-or more frequently if extruded-until ulcer resolution. Thirteen patients were studied. Mean age was 69 ± 6years and mean duration of menopause was 19 ± 6years. Nine patients had a single ulcer and four had multiple ulcers. Mean ulcer diameter was 2.8 ± 1.5cm and mean duration for ulcer healing was 26 ± 14days. Hysterectomy and pelvic floor reconstruction was performed a median of 5 (range 0-153) days after ulcer healing was first noted. Histopathological examination of the endometrium following hysterectomy showed three specimens with endocervical hyperplasia; one had concurrent proliferative endometrium, two had simple endometrial hyperplasia and another two had proliferative endometrium. Oestrogen-soaked vaginal packing is a viable option for managing a decubitus ulcer in advanced POP. We document a measurable impact on the endometrium with this short-term preoperative regimen. Further research is needed to evaluate its efficacy in promoting ulcer healing and endometrial safety.

Treatment of Chronic Graft Versus Host Disease with a Combination of B-Cell Depletion and Tyrosine Kinase Inhibition

Chronic Graft Versus Host Disease (cGVHD) affects about 60% of all patients receiving an allogeneic hematopoietic stem cell transplantation (HSCT) and surviving beyond day 100. Incidence of cGVHD is rising because of the widespread use of Peripheral Blood Stem Cells (PBSC) as stemcell source. Chronic GVHD accounts for high morbidity and mortality rates. Affected patients require long term use of immunosuppressive drugs, mainly corticosteroids, which lead to development of severe side effects. Both the manifestations of cGVHD as the side effects from immune suppressive drugs account for a decrease in quality of life when cGVHD develops. Therefor new therapeutic strategies are urgently needed.Therapeutic approaches for cGVHD are limited. Generally recommended first line therapy consists of glucocorticoid therapy combined with a calcineurin inhibitor. Options for second line therapy are numerous but no consensus on the most favourable choice of agents has been reached.However as both monotherapy with rituximab and monotherapy with tyrosine kinase inhibition have shown to be effective in reducing cGVHD symptoms . We aimed to test whether the sequential therapy of the anti CD20 antibody rituximab followed by a 6 month treatment period with the tyrosine kinase inhibitor nilotinib is a good treatment strategy for patients with sclerotic cGVHD (EudraCT nr 2008-004125-42).We treated 26 patients with a combination of 4 weekly infusions of rituximab followed by a 6 month period of treatment with nilotinib (300mg b.i.d.). Patients were evaluated monthly for 13 months and sequential blood samples and skin biopsies were analyzed. All patients gave informed consent before enrollment.3 patients experienced severe side effects from either rituximab or nilotinib treatment and therefor were taken off study. Of the remaining 13 patients who thus far have completed the study protocol, 60% showed a (partial) response (3 patients went from NIH scoring 'severe' to 'moderate', 1 patient went from NIH scoring 'moderate' to 'no cGVHD'). There is also a significant decrease in cGVHD affected body surface area (Figure 1). Moreover, two out of four patients who suffered from severe ulcerations at the start of the study had a complete resolution of ulcers at the end of the treatment period. Patients with a (partial) response also showed a decrease in self attributed severity of cGVHD and their immunosuppressive drugs could be tapered.The sequential therapy of B-cell depletion and tyrosine kinase inhibition provides a new and interesting alternative treatment option for this difficult and heavily pretreated patient category.Table 1Baseline characteristics of participants.Patients26Male sex20Mean age in years(range)47,521-70Primary diagnosisAML7Multiple myeloma5ALL4Lymphoma4MDS2CLL1Myeloproliferative disorder2aplastic anemia1Mean days after allo SCT(range)1368411-3820Ulcerative chronic GvHD at start5NIH grade severity cGVHD at startsevere20moderate6 [Display omitted] DisclosuresOff Label Use: Anti CD20 antibody rituximab is used for sclerotic chronic GVHD. Tyrosine kinase inhibitor nilotinib is used for sclerotic chronic GVHD..

Patient Outcomes and Factors Associated with Healing in Calciphylaxis Patients Undergoing Adjunctive Hyperbaric Oxygen Therapy

Calcific uremic arteriolopathy, also known as calciphylaxis, is a rare syndrome of small vessel calcification of unknown etiology causing painful, violaceous skin lesions that progress to form chronic non-healing ulcers and gangrene. Hyperbaric oxygen therapy (HBOT) can be used as adjunctive therapy in the treatment of these ulcers. However, due to paucity of cases, there is limited data on the clinical benefit of HBOT and identifying factors associated with healing. The purpose of this study was to determine patient outcomes and factors associated with healing in patients with calciphylaxis undergoing HBOT. A retrospective chart review was completed on patients who were diagnosed with calciphylaxis and had hyperbaric medicine consultation between May 2012 and January 2016. Clinical outcomes, demographics, risk factors, laboratory values, wound distribution, and HBOT profiles were collected and analyzed. We identified 8 patients. Out of 8 patients consulted for calciphylaxis, five were consented and underwent HBOT (2 males and 3 females). All had coexisting ESRD and Diabetes. All males were able to tolerate being in the chamber and received therapeutic treatments (at least 20 HBOT) with complete resolution of ulcers. HBOT was discontinued in one female due to an inconsistent biopsy report and two others due to death secondary to septic shock or respiratory arrest and severe uremia. Calciphylaxis is a devastating disease with a high mortality rate. Our results demonstrated a positive response to HBOT especially when receiving at least 20 treatments. A majority of calciphylaxis cases are females and indeed female gender has been cited as a risk factor for this disease. However, current literature has not conferred a relationship between gender nor the number of HBOT received and outcomes. Our results showed that males had a more favorable outcome provided they received at least twenty HBOT. Further prospective studies are needed to elucidate these outcomes.

Ustekinumab in the Successful Treatment of Refractory Esophageal Crohnʼs Disease: Presidential Poster

Esophageal involvement in Crohn disease (CD) is rare; a segment of this population is refractory to conventional CD therapies. Ustekinumab, a human monoclonal antibody against IL-12 and 23, is an emerging biologic agent in the management of patients with CD. Here we present a case of refractory esophageal CD that responded to ustekinumab. A 23 year old man presented for follow up of his CD complaining of odynophagia and oral ulcers. He had a 15 year history of aggressive, primarily stricturing colonic and perianal CD, status post subtotal colectomy with end ileostomy. Prior to colectomy, he failed conventional therapies including mesalamines, steroids, thiopurines, methotrexate, and anti-TNF agents; he also failed to respond to unconventional therapies including thalidomide, worms, GM-CSF, and stem cells. Post-operatively he did well on certolizumab pegol for a few years before the proximal alimentary tract symptoms occurred. Upper endoscopy revealed oral aphthae and multiple esophageal ulcers, biopsies showing ulceration and inflammation negative for viruses. Otolaryngology empirically treated for herpes simplex virus with valacyclovir and prednisone; symptoms rapidly improved but recurred after tapering off prednisone with poor oral intake leading to a 30 pound weight loss. He continued to have intermittent oral and esophageal symptoms despite high-dose prednisone, swallowed fluticasone, aggressive acid suppression, and certolizumab pegol. He declined natalizumab given JC virus positivity, vedolizumab was not yet approved and he did not meet study entry criteria, and thalidomide had previously led peripheral neuropathy. He was therefore switched from certolizumab pegol to ustekinumab at 90mg subcutaneously every 8 weeks; over the next several months he achieved prolonged symptom remission off all steroids and acid suppression. Repeat upper endoscopy revealed complete resolution of oral and esophageal ulceration (pre- and posttreatment in Figures 1 and 2 respectively).Figure 1Figure 2Ustekinumab has been shown to have promise in the treatment of refractory, typically intestinal CD [Gastroenterology 2008;135(4):1130-41. N Engl J Med 2012;367(16):1519-28]. To our knowledge, there are no prior reports on the successful use of ustekinumab in esophageal CD. We previously reported on the successful use of thalidomide for esophageal CD [Am J Gastroenterol 2013;108(5):855-7]. Most new therapies have focused on ileocolonic disease, including the anti-integrins; ustekinumab should be considered as a possible management strategy in patients with esophageal CD.

Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target.

The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program was initiated by the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD). It examined potential treatment targets for inflammatory bowel disease (IBD) to be used for a "treat-to-target" clinical management strategy using an evidence-based expert consensus process. A Steering Committee of 28 IBD specialists developed recommendations based on a systematic literature review and expert opinion. Consensus was gained if ≥75% of participants scored the recommendation as 7-10 on a 10-point rating scale (where 10=agree completely). The group agreed upon 12 recommendations for ulcerative colitis (UC) and Crohn's disease (CD). The agreed target for UC was clinical/patient-reported outcome (PRO) remission (defined as resolution of rectal bleeding and diarrhea/altered bowel habit) and endoscopic remission (defined as a Mayo endoscopic subscore of 0-1). Histological remission was considered as an adjunctive goal. Clinical/PRO remission was also agreed upon as a target for CD and defined as resolution of abdominal pain and diarrhea/altered bowel habit; and endoscopic remission, defined as resolution of ulceration at ileocolonoscopy, or resolution of findings of inflammation on cross-sectional imaging in patients who cannot be adequately assessed with ileocolonoscopy. Biomarker remission (normal C-reactive protein (CRP) and calprotectin) was considered as an adjunctive target. Evidence- and consensus-based recommendations for selecting the goals for treat-to-target strategies in patients with IBD are made available. Prospective studies are needed to determine how these targets will change disease course and patients' quality of life.

Sweet’s syndrome revealed by oral pustulosis

Introduction : Neutrophilic dermatoses are conditions characterized by a dermal neutrophilic infiltration associated with variable leukocytoclasia. Oral involvement occurs but is rare and is of less importance than the cutaneous involvement. Observation : The case of a 71-year-old man with neutrophilic dermatoses in whom the major manifestations of the disease were recurrent oral ulcers associated with tongue pustulosis is reported. Oral and skin biopsies revealed a dense neutrophilic infiltrate in the lamina propria. Clinical symptoms were quickly resolved with colchicine treatment. The clinical course allowed us to diagnose Sweet's syndrome associated with oral pustulosis. Discussion : The main differential diagnosis of Sweet's syndrome is from Behcet’s disease. Overlap exists between the manifestations of the two diseases, so they must be differentiated. The recurrence of oral ulcers with little inflammatory halo and the quick resolution of ulcers associated with pustules, as well as the histological patterns, were not compatible with Behcet's disease.

Effectiveness and cost-effectiveness of telephone-based support versus usual care for treatment of pressure ulcers in people with spinal cord injury in low-income and middle-income countries: study protocol for a 12-week randomised controlled trial

IntroductionPressure ulcers are a common and severe complication of spinal cord injury, particularly in low-income and middle-income countries where people often need to manage pressure ulcers alone and at home....

Factor XIII Transglutaminase Supports the Resolution of Mucosal Damage in Experimental Colitis

The thrombin-activated transglutaminase factor XIII (FXIII) that covalently crosslinks and stablizes provisional fibrin matrices is also thought to support endothelial and epithelial barrier function and to control inflammatory processes. Here, gene-targeted mice lacking the FXIII catalytic A subunit were employed to directly test the hypothesis that FXIII limits colonic pathologies associated with experimental colitis. Wildtype (WT) and FXIII-/- mice were found to be comparable in their initial development of mucosal damage following exposure to dextran sulfate sodium (DSS) challenge. However, unlike FXIII-sufficient mice, FXIII-deficient cohorts failed to efficiently resolve colonic inflammatory pathologies and mucosal damage following withdrawal of DSS. Consistent with prior evidence of ongoing coagulation factor activation and consumption in individuals with active colitis, plasma FXIII levels were markedly decreased in colitis-challenged WT mice. Treatment of colitis-challenged mice with recombinant human FXIII-A zymogen significantly mitigated weight loss, intestinal bleeding, and diarrhea, regardless of whether cohorts were FXIII-sufficient or were genetically devoid of FXIII. Similarly, both qualitative and quantitative microscopic analyses of colonic tissues revealed that exogenous FXIII improved the resolution of multiple colitis disease parameters in both FXIII-/- and WT mice. The most striking differences were seen in the resolution of mucosal ulceration, the most severe histopathological manifestation of DSS-induced colitis. These findings directly demonstrate that FXIII is a significant determinant of mucosal healing and clinical outcome following inflammatory colitis induced mucosal injury and provide a proof-of-principle that clinical interventions supporting FXIII activity may be a means to limit colitis pathology and improve resolution of mucosal damage.

Efficacy of intravenous immunoglobulins in livedoid vasculopathy: Long-term follow-up of 11 patients

Evidence for the efficacy of various therapies of livedoid vasculopathy (LV) is limited. We sought to determine efficacy and tolerability of 2 g/kg of intravenous immunoglobulins (IVIG) every 4 weeks in patients with LV. This was a long-term follow-up study of 11 patients with LV treated with 2 g/kg of IVIG assessing the clinical characteristics, disease course, and quality of life. The treatment regimen led to complete remission of ulcerations and pain in 17 of 29 disease episodes (59%) after 3 cycles and in 25 of 29 episodes (86%) after 6 cycles. Two disease episodes showed remission after 7 and 8 cycles, resulting in a total number of remissions of 27 (93%). Subscore analysis showed resolution of pain in 80% after 2 IVIG cycles. Disease severity and quality of life were significantly improved after 6 cycles. Median duration of remissions was 26.7 months after initial and 7.5 months after subsequent disease episodes. This was a retrospective study that did not include the comparison of IVIG efficacy and its impact on quality of life with treatment options. In our patients with LV, high-dose IVIG led to fast and complete resolution of pain and ulcerations and to substantial improvement in quality of life.

Infliximab maintains durable response and facilitates catch-up growth in luminal pediatric Crohn's disease.

Infliximab induces and maintains clinical remission in children with Crohn's disease (CD), but specifically pediatric long-term data remain sparse. Patients (N = 195) who received infliximab ± immunomodulator for luminal CD were retrospectively reviewed. Outcomes included clinical response, linear growth, and mucosal healing. Durability of response was assessed using Cox proportional hazards models. Levels of infliximab and antibodies (antibodies to infliximab) were measured when response was lost. Among 195 patients (median age, 13.9 yr; median CD duration, 1.6 yr), 81% experienced complete response (judged by physician global assessment and pediatric Crohn's disease activity index ≤10). Longer duration of diagnosed CD and female gender were associated with lower response. During first year of follow-up, 35% of subjects had regimen individualized through dose escalation/interval shortening. Despite regimen optimization, 16/157 complete responders experienced loss of response at a rate of 2% to 6% per year over 5 years, associated with development of antibodies to infliximab. Concurrent immunomodulation for ≥30 weeks significantly decreased loss of response (hazard ratio = 0.25, 95% confidence interval, 0.08-0.76; P = 0.014). Follow-up endoscopic examination was performed in 40 responders, of whom 22 (73%) demonstrated complete resolution of mucosal ulceration. Patients with growth potential (Tanner 1/2 at induction) demonstrated significant improvements in mean height z-score from induction to years 1 and 2 of follow-up (P < 0.001). With infliximab initiation within the first 18 months after diagnosis, mean height z-score normalized to 0 after 3 years. These data demonstrate sustained effectiveness of infliximab in children and adolescents with luminal CD. Durability of response is increased by concomitant immunomodulation. Clinical response is associated with enhanced linear growth, particularly when therapy is initiated early.

Etanercept induces remission of polyarteritis nodosa: a case report.

Etanercept induces remission of polyarteritis nodosa: a case report.